MI Linked to Increased Vascular Dementia, Not Alzheimer's

A history of MI is associated with an increased risk of vascular dementia by as much as 35%, with the higher risk extending as far as 35 years after the event, results of a population-based study suggest[1].

"We have demonstrated for the first time that patients surviving a heart attack have increased risk of vascular dementia, but not increased risk of Alzheimer's disease and other dementia subtypes," senior author Dr Jens Sundbøll (Aarhus University Hospital, Denmark) told theheart.org | Medscape Cardiology.

"This is the largest study of its kind and the first also to consider important subgroups of dementia," he said.

The study was published in Circulation.

The analysis included 314,911 patients in the Danish National Patient Registry who suffered a first-time MI between 1980 and 2012 who were matched by sex, birth year, and calendar year with a general population cohort of 1,573,193 subjects without a history of MI.

The subjects had a median age of 70 years and 63% were male.

Follow-up for dementia diagnoses through the Danish Psychiatric Central Research Register at a median of 7.7 years in the MI group and 9.8 years in the comparison cohort showed that 8.7% of patients developed dementia overall, with 2.8% developing Alzheimer's disease, 1.6% developing vascular dementia, and 4.5% with other dementias.

Having had an MI was associated with an increased risk of vascular dementia (adjusted hazard ratio [HR] 1.35) vs the comparison group, with the risk substantially higher among patients who experienced stroke following the MI (adjusted HR 4.48).

A history of MI was not significantly linked to a risk of Alzheimer's disease (adjusted HR 0.92) or other dementias (adjusted HR 0.98).

The authors noted that the difference in median follow-up times between the two groups was largely related to the increased risk of death following MI.

Other factors that were linked to an increased risk of vascular dementia included having undergone bypass surgery following the MI, which increased the risk by as much as fourfold (adjusted HR 3.99); however, undergoing balloon angioplasty was not linked to an increased vascular dementia risk.

Likewise, pacemaker implantation also was linked to an increased risk of vascular dementia (adjusted HR 3.38). Atrial fibrillation or flutter was associated with only a moderately higher risk of vascular dementia (adjusted HR 1.55).

In speculating on mechanisms explaining the risk, the authors note that key shared risk factors of heart attack and vascular dementia, including hypertension, diabetes, and smoking, likely play a role in the long term.

"Atherosclerosis may be the underlying factor driving the development of myocardial infarction, ischemic stroke, and, ultimately, vascular dementia, but with a longer latency period for vascular dementia," the authors write.

"In support of this assumption, only risk of vascular dementia was higher in our study."

Atrial fibrillation and regional wall-motion abnormalities could also play a role, Sundbøll explained.

"[The abnormalities] in the left ventricle facilitating the formation of intracardiac thrombi can embolize to the brain and cause vascular dementia," he said.

Hypoperfusion to the brain following an MI is likely also a mediator, with low blood pressure possibly linked to infarctions in susceptible areas of the brain, and even the post-MI therapeutic regimen could increase the risk, Sundbøll noted.

"The aggressive antithrombotic regimen after heart attack increases the risk of intracerebral hemorrhages, which also can lead to vascular dementia."

The study showed a progressively smaller increment of risk for all subtypes of dementia with increasing age, which "may reflect that many individuals with a heavy burden of cardiovascular risk factors do not survive to old age," the authors write.

While the study doesn't describe preventive measures, Sundbøll said the findings should serve as a wake-up call for clinicians.

"The take-home message from this should be that among 1-year survivors of myocardial infarction, attention to the persistently higher risk of vascular dementia is important," he said.

While the effect of any formal screening for cognitive decline is unclear, opportunistic screening, when relevant, seems prudent, Sundbøll added.

"Even though vascular dementia only makes up 20% of all dementia cases, the potential to prevent these cases is huge," he said, "especially looking forward, as all Western societies face a demographic shift toward an elderly population in the coming decades."

Commenting on the study, Dr Steven T DeKosky (McKnight Brain Institute, University of Florida, Gainesville) said the lack of an association between MI and Alzheimer's disease was a surprise.

"Based on the neuropathology data we have, many of the cases diagnosed as Alzheimer's disease clinically also have significant vascular pathology," he told theheart.org | Medscape Cardiology.
"So we might expect a relationship of MI with Alzheimer's disease as well as vascular dementia."

He noted that an important factor not included in the data set was the status of ApoE genotype, known to increase the risk of Alzheimer's disease.

"It might help provide additional information about the likelihood of accuracy of the Alzheimer's disease diagnosis, [including] in the [unspecified] dementia group."

In addition, various pathologies in vascular dementia need more consideration, said DeKosky, who is a Fellow of the American Academy of Neurology.

"Within vascular dementia there are several different kinds of pathologies at work, [such as] large infarctions and small infarctions in key areas associated with memory or conditions for attention, or microinfarctions."

The study should nevertheless help advance the understanding of the longer-term vascular risks associated with MI, he said.

"Large retrospective studies such as this one should point the way for prospective studies, and the findings should lead to increased focus on MI as evidence for an increased risk of vascular dementia and for being able to categorize the type of vascular dementia that develops in the group of affected people," DeKosky said.

"Given that we do have ways to modify the vascular risk, this area of inquiry is extremely valuable.

"I think the outcome of the study will provide additional evidence that people with MIs should be treated aggressively and watched carefully for emergencies of clinical symptoms."